tbuckley/cabot-search huggingface dataset:
Diversification of Ubiquinone Biosynthesis via Gene Duplications, Transfers, Losses, and Parallel Evolution
Authors: Katayoun Kazemzadeh, Ludovic Pelosi, Clothilde Chenal, Sophie-Carole Chobert, Mahmoud Hajj Chehade, Margaux Jullien, Laura Flandrin, William Schmitt, Qiqi He, Emma Bouvet, Manon Jarzynka, Nelle Varoquaux, Ivan Junier, Fabien Pierrel, Sophie S Abby
Journal: Molecular Biology and Evolution (2023)

The availability of an ever-increasing diversity of prokaryotic genomes and metagenomes represents a major opportunity to understand and decipher the mechanisms behind the functional diversification of microbial biosynthetic pathways. However, it remains unclear to what extent a pathway producing a specific molecule from a specific precursor can diversify. In this study, we focus on the biosynthesis of ubiquinone (UQ), a crucial coenzyme that is central to the bioenergetics and to the functioning of a wide variety of enzymes in Eukarya and Pseudomonadota (a subgroup of the formerly named Proteobacteria). UQ biosynthesis involves three hydroxylation reactions on contiguous carbon atoms. We and others have previously shown that these reactions are catalyzed by different sets of UQ-hydroxylases that belong either to the iron-dependent Coq7 family or to the more widespread flavin monooxygenase (FMO) family. Here, we combine an experimental approach with comparative genomics and phylogenetics to reveal how UQ-hydroxylases evolved different selectivities within the constrained framework of the UQ pathway. It is shown that the UQ-FMOs diversified via at least three duplication events associated with two cases of neofunctionalization and one case of subfunctionalization, leading to six subfamilies with distinct hydroxylation selectivity. We also demonstrate multiple transfers of the UbiM enzyme and the convergent evolution of UQ-FMOs toward the same function, which resulted in two independent losses of the Coq7 ancestral enzyme. Diversification of this crucial biosynthetic pathway has therefore occurred via a combination of parallel evolution, gene duplications, transfers, and losses.
A Sonoresponsive and NIR‐II‐Photoresponsive Nanozyme for Heterojunction‐Enhanced “Three‐in‐One” Multimodal Oncotherapy
Authors: Lang Yan, Zhi Cao, Lijun Ren, Tiantian Zhang, Jinyan Hu, Jikuai Chen, Xiaofang Zhang, Bing Liu, Chuanqi Feng, Jiangbo Zhu, Bijiang Geng
Journal: Advanced Healthcare Materials (2023)

Abstract Although low‐cost nanozymes with excellent stability have demonstrated the potential to be highly beneficial for nanocatalytic therapy (NCT), their unsatisfactory catalytic activity accompanied by intricate tumor microenvironment (TME) significantly hinders the therapeutic effect of NCT. Herein, for the first time, a heterojunction (HJ)‐fabricated sonoresponsive and NIR‐II‐photoresponsive nanozyme is reported by assembling carbon dots (CDs) onto TiCN nanosheets. The narrow bandgap and mixed valences of Ti 3+ and Ti 4+ endow TiCN with the capability to generate reactive oxygen species (ROS) when exposed to ultrasound (US), as well as the dual enzyme‐like activities of peroxidase and glutathione peroxidase. Moreover, the catalytic activities and sonodynamic properties of the TiCN nanosheets are boosted by the formation of HJs owing to the increased speed of carrier transfer and the enhanced electron–hole separation. More importantly, the introduction of CDs with excellent NIR‐II photothermal properties could achieve mild hyperthermia (43 °C) and thereby further improve the NCT and sonodynamic therapy (SDT) performances of CD/TiCN. The synergetic therapeutic efficacy of CD/TiCN through mild hyperthermia‐amplified NCT and SDT could realize “three‐in‐one” multimodal oncotherapy to completely eliminate tumors without recurrence. This study opens a new avenue for exploring sonoresponsive and NIR‐II‐photoresponsive nanozymes for efficient tumor therapy based on semiconductor HJs.
Hidradenitis suppurativa in the elderly: new insights
Authors: Jonathan M White, Véronique Del Marmol
Journal: British Journal of Dermatology (2023)

Journal Article Accepted manuscript Hidradenitis suppurativa in the elderly: new insights Get access Jonathan M White, Jonathan M White Department of Dermatology, Erasme Hospital, Brussels, BelgiumEcole de Santé Publique, Université libre de Bruxelles, Belgium Search for other works by this author on: Oxford Academic Google Scholar Véronique Del Marmol Véronique Del Marmol Department of Dermatology, Erasme Hospital, Brussels, Belgium Corresponding author: Prof Véronique Del Marmol Email:Veronique.DelMarmol@hubruxelles.be Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad378, https://doi.org/10.1093/bjd/ljad378 Published: 04 October 2023 Article history Received: 20 September 2023 Accepted: 02 October 2023 Published: 04 October 2023
On cooperative libertines and wicked puritans
Authors: Roger Giner-Sorolla, Simon Myers
Journal: Behavioral and Brain Sciences (2023)

Abstract We agree with Fitouchi et al. that self-denial is sometimes moralized to signal capacity for cooperation, but propose that a person's cooperative character is more precisely judged by willingness to follow cultural, group, and interpersonal goals, for which many rules can serve as proxies, including rules about abstention. But asceticism is not a moral signal if its aims are destructive, while indulging impulses in a culturally approved way can also signal cooperation.
Puritanical morality and the scaffolded evolution of self-control
Authors: Walter Veit, Heather Browning
Journal: Behavioral and Brain Sciences (2023)

Abstract There is a puzzle in reconciling the widespread presence of puritanical norms condemning harmless pleasures with the theory that morality evolved to reap the benefits of cooperation. Here, we draw on the work of several philosophers to support the argument by Fitouchi et al. that these norms evolved to facilitate and scaffold self-control for the sake of cooperation.
Puritanism needs purity, and moral psychology needs pluralism
Authors: Jesse Graham, Mohammad Atari, Morteza Dehghani, Jonathan Haidt
Journal: Behavioral and Brain Sciences (2023)

Abstract This account of puritanical morality is useful and innovative, but makes two errors. First, it mischaracterizes the purity foundation as being unrelated to cooperation. Second, it makes the leap from cooperation (broadly construed) to a monist account of moral cognition (as harm or fairness). We show how this leap is both conceptually incoherent and inconsistent with empirical evidence about self-control moralization.
Age and associated outcomes among patients receiving venoarterial extracorporeal membrane oxygenation–analysis of the Extracorporeal Life Support Organization registry
Authors: Shannon M. Fernando, Graeme MacLaren, Ryan P. Barbaro, Rebecca Mathew, Laveena Munshi, Purnema Madahar, Justin A. Fried, Kollengode Ramanathan, Roberto Lorusso, Daniel Brodie, Daniel I. McIsaac
Journal: Intensive Care Medicine (2023)
The puritanical moral contract: Purity, cooperation, and the architecture of the moral mind
Authors: Léo Fitouchi, Jean-Baptiste André, Nicolas Baumard
Journal: Behavioral and Brain Sciences (2023)

Abstract Commentators raise fundamental questions about the notion of purity (sect. R1), the architecture of moral cognition (sect. R2), the functional relationship between morality and cooperation (sect. R3), the role of folk-theories of self-control in moral judgment (sect. R4), and the cultural variation of morality (sect. R5). In our response, we address all these issues by clarifying our theory of puritanism, responding to counter-arguments, and incorporating welcome corrections and extensions.
Motor Vehicle Crash Risk in Older Adult Drivers With Attention-Deficit/Hyperactivity Disorder
Authors: Yuxin Liu, Stanford Chihuri, Thelma J. Mielenz, Howard F. Andrews, Marian E. Betz, Carolyn DiGuiseppi, David W. Eby, Linda L. Hill, Vanya Jones, Lisa J. Molnar, David Strogatz, Guohua Li
Journal: JAMA Network Open (2023)

Symptoms of attention-deficit/hyperactivity disorder (ADHD), such as inattentiveness and impulsivity, could affect daily functioning and driving performance throughout the life span. Previous research on ADHD and driving safety is largely limited to adolescents and young adults.To examine the prevalence of ADHD and the association between ADHD and crash risk among older adult drivers.This prospective cohort study collected data from primary care clinics and residential communities in 5 US sites (Ann Arbor, Michigan; Baltimore, Maryland; Cooperstown, New York; Denver, Colorado; and San Diego, California) between July 6, 2015, and March 31, 2019. Participants were active drivers aged 65 to 79 years at baseline enrolled in the Longitudinal Research on Aging Drivers project who were studied for up to 44 months through in-vehicle data recording devices and annual assessments. The data analysis was performed between July 15, 2022, and August 14, 2023.Lifetime ADHD based on an affirmative response to the question of whether the participant had ever had ADHD or had ever been told by a physician or other health professional that he or she had ADHD.The main outcomes were hard-braking events defined as maneuvers with deceleration rates of 0.4g or greater, self-reported traffic ticket events, and self-reported vehicular crashes. Multivariable negative binomial modeling was used to estimate adjusted incidence rate ratios (aIRRs) and 95% CIs of outcomes according to exposure status.Of the 2832 drivers studied, 1500 (53.0%) were women and 1332 (47.0%) were men with a mean (SD) age of 71 (4) years. The lifetime prevalence of ADHD in the study sample was 2.6%. Older adult drivers with ADHD had significantly higher incidence rates of hard-braking events per 1000 miles than those without ADHD (1.35 [95% CI, 1.30-1.41] vs 1.15 [95% CI, 1.14-1.16]), as well as self-reported traffic ticket events per 1 million miles (22.47 [95% CI, 16.06-31.45] vs 9.74 [95% CI, 8.99-10.55]) and self-reported vehicular crashes per 1 million miles (27.10 [95% CI, 19.95-36.80] vs 13.50 [95% CI, 12.61-14.46]). With adjustment for baseline characteristics, ADHD was associated with a significant 7% increased risk of hard-braking events (aIRR, 1.07; 95% CI, 1.02-1.12), a 102% increased risk of self-reported traffic ticket events (aIRR, 2.02; 95% CI, 1.42-2.88), and a 74% increased risk of self-reported vehicular crashes (aIRR, 1.74; 95% CI, 1.26-2.40).As observed in this prospective cohort study, older adult drivers with ADHD may be at a significantly elevated crash risk compared with their counterparts without ADHD. These findings suggest that effective interventions to improve the diagnosis and clinical management of ADHD among older adults are warranted to promote safe mobility and healthy aging.
Advances in Melanoma-Nevus Classification Using Artificially Generated Image Data Sets
Authors: Titus J. Brinker
Journal: JAMA Dermatology (2023)

The challenging task of skin cancer classification via artificial intelligence (AI) is a combined effort of dermatologists, patients, and the machine-learning community.1,2 A classifier in this case is a software based on AI that assigns skin photographs to categories (ie, benign or malignant).
Effects of Bundling Medication for Opioid Use Disorder With an mHealth Intervention Targeting Addiction: A Randomized Clinical Trial
Authors: David H. Gustafson, Gina Landucci, Olivia J. Vjorn, Rachel E. Gicquelais, Simon B. Goldberg, Darcie C. Johnston, John J. Curtin, Genie L. Bailey, Dhavan V. Shah, Klaren Pe-Romashko, David H. Gustafson
Journal: American Journal of Psychiatry (2023)

Objective: Medication for opioid use disorder (MOUD) improves treatment retention and reduces illicit opioid use. A-CHESS is an evidence-based smartphone intervention shown to improve addiction-related behaviors. The authors tested the efficacy of MOUD alone versus MOUD plus A-CHESS to determine whether the combination further improved outcomes. Methods: In an unblinded parallel-group randomized controlled trial, 414 participants recruited from outpatient programs were assigned in a 1:1 ratio to receive either MOUD alone or MOUD+A-CHESS for 16 months and were followed for an additional 8 months. All participants were on methadone, buprenorphine, or injectable naltrexone. The primary outcome was abstinence from illicit opioid use; secondary outcomes were treatment retention, health services use, other substance use, and quality of life; moderators were MOUD type, gender, withdrawal symptom severity, pain severity, and loneliness. Data sources were surveys comprising multiple validated scales, as well as urine screens, every 4 months. Results: There was no difference in abstinence between participants in the MOUD+A-CHESS and MOUD-alone arms across time (odds ratio=1.10, 95% CI=0.90–1.33). However, abstinence was moderated by withdrawal symptom severity (odds ratio=0.95, 95% CI=0.91–1.00) and MOUD type (odds ratio=0.57, 95% CI=0.34–0.97). Among participants without withdrawal symptoms, abstinence rates were higher over time for those in the MOUD+A-CHESS arm than for those in the MOUD-alone arm (odds ratio=1.30, 95% CI=1.01–1.67). Among participants taking methadone, those in the MOUD+A-CHESS arm were more likely to be abstinent over time (b=0.28, SE=0.09) than those in the MOUD-alone arm (b=0.06, SE=0.08), although the two groups did not differ significantly from each other (∆b=0.22, SE=0.11). MOUD+A-CHESS was also associated with greater meeting attendance (odds ratio=1.25, 95% CI=1.05–1.49) and decreased emergency department and urgent care use (odds ratio=0.88, 95% CI=0.78–0.99). Conclusions: Overall, MOUD+A-CHESS did not improve abstinence relative to MOUD alone. However, MOUD+A-CHESS may provide benefits for subsets of patients and may impact treatment utilization.
Prevalence and Trends in Diagnosed ADHD Among US Children and Adolescents, 2017-2022
Authors: Yanmei Li, Xiaofang Yan, Qishan Li, Qian Li, Guifeng Xu, Jinhua Lu, Wenhan Yang
Journal: JAMA Network Open (2023)

This cross-sectional study estimates prevalence and trends of ADHD diagnosis among US children and adolescents from 2017 to 2022.
Tumor-Agnostic Approvals: Insights and Practical Considerations
Authors: Chengxing Cindy Lu, Robert A. Beckman, Xiaoyun Nicole Li, Weidong Zhang, Qi Jiang, Olga Marchenko, Zhiping Sun, Hong Tian, Jingjing Ye, Shuai Sammy Yuan, Godwin Yung
Journal: Clinical Cancer Research (2023)

Abstract Since the first approval of a tumor-agnostic indication in 2017, a total of seven tumor-agnostic indications involving six drugs have received approval from the FDA. In this paper, the master protocol subteam of the Statistical Methods in Oncology Scientific Working Group, Biopharmaceutical Session, American Statistical Association, provides a comprehensive summary of these seven tumor-agnostic approvals, describing their mechanisms of action; biomarker prevalence; study design; companion diagnostics; regulatory aspects, including comparisons of global regulatory requirements; and health technology assessment approval. Also discussed are practical considerations relating to the regulatory approval of tumor-agnostic indications, specifically (i) recommendations for the design stage to mitigate the risk that exceptions may occur if a treatment is initially hypothesized to be effective for all tumor types and (ii) because drug development continues after approval of a tumor-agnostic indication, recommendations for further development of tumor-specific indications in first-line patients in the setting of a randomized confirmatory basket trial, acknowledging the challenges in this area. These recommendations and practical considerations may provide insights for the future development of drugs for tumor-agnostic indications.
Little puritans?
Authors: Christina Starmans
Journal: Behavioral and Brain Sciences (2023)

Abstract I propose that young children may be a useful test case for Fitouchi et al.'s theory that certain seemingly harmless acts are moralized because they are seen as risk factors for future poor cooperation. The theory predicts that prior to the development of certain folk-psychological beliefs about self-control, children should be untroubled by violations of puritanical morality, and that an adult-like folk psychology of self-control should develop in tandem with disapproval of such violations.
Prevalence of Autism Among Medicaid-Enrolled Adults
Authors: Eric Rubenstein, Salina Tewolde, Amy Michals, Matthew Fox, Na Wang
Journal: JAMA Psychiatry (2023)

Importance The reported prevalence of autism in children has consistently risen over the past 20 years. The concurrent implications for the adult Medicaid system, which insures autistic adults due to low income or disability, have not been studied. Objective To estimate the prevalence of adults identified as autistic in Medicaid claims data and to examine the prevalence by year, age, and race and ethnicity to understand enrollment patterns. Design, Setting, and Participants This cohort study used data from a longitudinal Medicaid claims cohort of enrollees aged 18 years or older with a claim for autism at any point from January 1, 2011, to December 31, 2019, and an approximately 1% random sample of all adult Medicaid enrollees. The data were analyzed between February 22 and June 22, 2023. Exposure Adults enrolled in Medicaid with a claim for autism. Main Outcome and Measures Prevalence of autism per 1000 Medicaid enrollees for each year was calculated using denominator data from the Centers for Medicare &amp;amp;amp; Medicaid Services weighted to nondisabled population demographic characteristics. Prevalence by race and ethnicity were calculated for study year 2019. Results Across 9 years, 403 028 unique adults had autism claims in their Medicaid records (25.7% female, 74.2% male, 3.3% Asian, 16.8% Black, 12.2% Hispanic, 0.8% Native American, 0.8% Pacific Islander, 74.3% White, and 4.2% of multiple races). Across all ages, autism prevalence increased from 4.2 per 1000 enrollees in 2011 to 9.5 per 1000 enrollees in 2019. The largest increase over the 9 years was in the 25- to 34-year age group (195%), and the smallest increase was in the 55- to 64-year age group (45%). The prevalence of White enrollees was at least 2 times that of the prevalence of every other racial group in all age categories. Conclusions and Relevance The study findings suggest that despite difficulties in identifying autism in adults, there is a considerable and growing population of autistic adults enrolled in Medicaid. As children on the autism spectrum become autistic adults, Medicaid is an important insurance provider for an increasing number of autistic adults and can be a valuable resource for understanding the health of the autistic population.
Moral disciplining provides a satisfying explanation for Chinese lay concepts of immorality
Authors: Emma E Buchtel
Journal: Behavioral and Brain Sciences (2023)

Abstract In our research on lay prototypes of immorality, we found that Chinese consider immoral behaviors to be more about showing coarse character, rather than being violent and harmful (called criminal behaviors). The target article provides a satisfying rationale for why this Chinese immorality concept, which has many similarities to the puritanical morality described here, is connected to the morality of cooperation.
The many faces of moralized self-control: Puritanical morality is not reducible to cooperation concerns
Authors: Netanel Y Weinstein, Dare A Baldwin
Journal: Behavioral and Brain Sciences (2023)

Abstract Fitouchi et al.'s moral disciplining approach highlights the significant role social evaluations of self-control appear to play in human moral judgment. At the same time, attributing the wide range of puritanical concerns to a singular focus on self-control seems unwarranted. A more pluralistic approach would enrich understanding of moral judgment in all its cultural and historical diversity.
Generation of a Melanoma and Nevus Data Set From Unstandardized Clinical Photographs on the Internet
Authors: Soo Ick Cho, Cristian Navarrete-Dechent, Roxana Daneshjou, Hye Soo Cho, Sung Eun Chang, Seong Hwan Kim, Jung-Im Na, Seung Seog Han
Journal: JAMA Dermatology (2023)

Importance Artificial intelligence (AI) training for diagnosing dermatologic images requires large amounts of clean data. Dermatologic images have different compositions, and many are inaccessible due to privacy concerns, which hinder the development of AI. Objective To build a training data set for discriminative and generative AI from unstandardized internet images of melanoma and nevus. Design, Setting, and Participants In this diagnostic study, a total of 5619 (CAN5600 data set) and 2006 (CAN2000 data set; a manually revised subset of CAN5600) cropped lesion images of either melanoma or nevus were semiautomatically annotated from approximately 500 000 photographs on the internet using convolutional neural networks (CNNs), region-based CNNs, and large mask inpainting. For unsupervised pretraining, 132 673 possible lesions (LESION130k data set) were also created with diversity by collecting images from 18 482 websites in approximately 80 countries. A total of 5000 synthetic images (GAN5000 data set) were generated using the generative adversarial network (StyleGAN2-ADA; training, CAN2000 data set; pretraining, LESION130k data set). Main Outcomes and Measures The area under the receiver operating characteristic curve (AUROC) for determining malignant neoplasms was analyzed. In each test, 1 of the 7 preexisting public data sets (total of 2312 images; including Edinburgh, an SNU subset, Asan test, Waterloo, 7-point criteria evaluation, PAD-UFES-20, and MED-NODE) was used as the test data set. Subsequently, a comparative study was conducted between the performance of the EfficientNet Lite0 CNN on the proposed data set and that trained on the remaining 6 preexisting data sets. Results The EfficientNet Lite0 CNN trained on the annotated or synthetic images achieved higher or equivalent mean (SD) AUROCs to the EfficientNet Lite0 trained using the pathologically confirmed public data sets, including CAN5600 (0.874 [0.042]; P = .02), CAN2000 (0.848 [0.027]; P = .08), and GAN5000 (0.838 [0.040]; P = .31 [Wilcoxon signed rank test]) and the preexisting data sets combined (0.809 [0.063]) by the benefits of increased size of the training data set. Conclusions and Relevance The synthetic data set in this diagnostic study was created using various AI technologies from internet images. A neural network trained on the created data set (CAN5600) performed better than the same network trained on preexisting data sets combined. Both the annotated (CAN5600 and LESION130k) and synthetic (GAN5000) data sets could be shared for AI training and consensus between physicians.
Increasing Proportion of Visits Delivered by NPs, PAs
Authors: Emily Harris
Journal: JAMA (2023)

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